Energy Transfer in functionalized carbon nanotubes

Tailoring the properties of carbon nanotubes by chemical functionalization is one of the key challenges towards the realization of carbon nanotube-based opto-electronic devices. This technique aims at combining the great transport properties of nanotubes with the versatility of the optical properties of organic molecules. We present new results about "pi-stacking" functionalization of single wall carbon nanotubes with porphyrin molecules. The optical properties of these complexes are investigated by means of photoluminescence excitation and ultrafast pump/probe experiments. The nanotubes/porphyrin complexes show a total quenching of the porphyrin fluorescence, while the luminescence of the nanotubes is preserved and even enhanced when the excitation is tuned in resonance with the Soret band of the porphyrins. This brings evidence for an efficient energy transfer within the nanotube/porphyrin complex, which corresponds to the implementation of a key functionality: an organic graft acting as an antenna and the nanotube acting as a collector. The dynamics of this transfer turn out to be extremely fast, in qualitative agreement with the high transfer ratio observed in permanent regime

Nanotubes-Porphyrine suspensions optimisation for energy transfer

Chemical functionalization of carbon nanotubes is one of the key challenges towards their use in opto-electronic devices. This technique aims at combining the great transport properties of nanotubes with the versatility of the optical properties of organic molecules. “π-stacking” functionalization of single wall carbon nanotubes with porphyrin molecules has been achieved and energy transfer has been observed from the molecules to the nanotubes by means of luminescence experiments. Nevertheless, these first trials have been performed on suspensions presenting poor stability and low photoluminescence yield. We present here a new process of functionalization that enhances the properties of these suspensions. First, the new suspensions are now stable for months ( as compared with a few days in previous works). The luminescence of these suspensions is also enhanced by more than one order of magnitude in comparison with reference. The good stability and the high luminescence yield will allow more detailed study of the electronic processes occuring in these complexes. Secondly, the nanotubes luminescence is preserved when they are deposited on a surface demonstrating that porphyrin molecules act as a protection shield for the tubes. This latter property is very interesting in view of applications such as photovoltaic cells or fundamental studie

Verifying and Validating Quantitative Systems Pharmacology and In Silico Models in Drug Development: Current Needs, Gaps, and Challenges

The added value of in silico models (including quantitative systems pharmacology models) for drug development is now unanimously recognized. It is, therefore, important that the standards used are commonly acknowledged by all the parties involved. On April 25 and 26, 2019, a multistakeholder workshop on the validation challenges for in silico models in drug development was organized in Belgium. As an outcome, a White Paper is foreseen in 2020 on standards for in silico model verification and validation.status: publishe

Possible Contexts of Use for in Silico Trials Methodologies: A Consensus-Based Review

none18siThe term 'In Silico Trial' indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative.noneViceconti M.; Emili L.; Afshari P.; Courcelles E.; Curreli C.; Famaey N.; Geris L.; Horner M.; Jori M.C.; Kulesza A.; Loewe A.; Neidlin M.; Reiterer M.; Rousseau C.F.; Russo G.; Sonntag S.J.; Voisin E.M.; Pappalardo F.Viceconti M.; Emili L.; Afshari P.; Courcelles E.; Curreli C.; Famaey N.; Geris L.; Horner M.; Jori M.C.; Kulesza A.; Loewe A.; Neidlin M.; Reiterer M.; Rousseau C.F.; Russo G.; Sonntag S.J.; Voisin E.M.; Pappalardo F

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation. To properly frame the proposed verification and validation activities, concepts such as context of use, regulatory impact and risk-based analysis are discussed. To ensure common understanding between all stakeholders, an overview is provided of relevant in silico terminology used throughout this paper. To illustrate the feasibility of the proposed approach, we have applied it to three real case examples in the context of drug development, using a credibility matrix currently being tested as a quick-start tool by regulators. Altogether, this white paper provides a practical approach to model evaluation, applicable in both scientific and regulatory evaluation contexts

Scientific and regulatory evaluation of mechanistic in silico

Abstract The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk‐informed evaluation framework for mechanistic model credibility evaluation. To properly frame the proposed verification and validation activities, concepts such as context of use, regulatory impact and risk‐based analysis are discussed. To ensure common understanding between all stakeholders, an overview is provided of relevant in silico terminology used throughout this paper. To illustrate the feasibility of the proposed approach, we have applied it to three real case examples in the context of drug development, using a credibility matrix currently being tested as a quick‐start tool by regulators. Altogether, this white paper provides a practical approach to model evaluation, applicable in both scientific and regulatory evaluation contexts

Nature genetics

Study of monogenic forms of obesity has demonstrated the pivotal role of the central leptin-melanocortin pathway in controlling energy balance, appetite and body weight (1) . The majority of loss-of-function mutations (mostly recessive or co-dominant) have been identified in genes that are directly involved in leptin-melanocortin signaling. These genes, however, only explain obesity in <5% of cases, predominantly from outbred populations (2) . We previously showed that, in a consanguineous population in Pakistan, recessive mutations in known obesity-related genes explain ~30% of cases with severe obesity(3-5). These data suggested that new monogenic forms of obesity could also be identified in this population. Here we identify and functionally characterize homozygous mutations in the ADCY3 gene encoding adenylate cyclase 3 in children with severe obesity from consanguineous Pakistani families, as well as compound heterozygous mutations in a severely obese child of European-American descent. These findings highlight ADCY3 as an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity